The effect of derivatives of sulfur-containing amino acids (ademetionine, taurine and glutathione) on survival of animals with acute kidney injury of various genesis

V. M. Drachuk, I. I. Zamorskii, T. S. Shchudrova, Ol. M. Goroshko

Abstract

Aim. To study the nephroprotective effect of sulfur-containing amino acids (ademetionine, taurine and glutathione) on different models of acute kidney injury (AKI) by the integral index of the survival rate of animals.

Materials and methods. The experiments were performed on 105 non-linear mature white laboratory rats and 35 mice. The drugs studied – ademetionine (Geptral, Abbott SpA, Italy) in the dose of 20 mg/kg, glutathione (TAD 600, Biomedica Foscama, Italy) in the dose of 30 mg/kg and taurine (Sigma-Aldrich, USA) in the dose of dose 100 mg/kg – were injected intraperitoneally 3-7 days before AKI modeling. Rhabdomyolysis-induced AKI was modeled by the intramuscular injection of 50 % glycerol solution in the dose of 10 ml/kg, toxic AKI – by the injection of gentamicin solution in the dose of 80 mg/kg and the subcutaneous injection of ethylene glycol in the dose of 10 ml/kg. Simulation of renal ischemia was performed under general anesthesia (ethaminal sodium, 40 mg/kg) by clamping of both renal pedicles for a period of 60 min, followed by reperfusion for 24 h.

Results and discusion. The experimental results show a significant improvement in the survival of animals under the effect of the drugs of derivatives of sulfur-containing amino acids studied in conditions of various models of AKI. Ademetionine, taurine and glutathione reduced the lethality of animals on models of rhabdomyolytic, gentamicin, ischemia-reperfusion AKI. In conditions of ethylene glycol intoxication the highest nephroprotective activity by the survival criterion was shown by glutathione (57.1 % survival at 48 h after administration of ethylene glycol against 100 % of mortality in the control group (p < 0.05).

Conclusions. All derivatives of sulfur-containing amino acids studied (ademetionine, taurine and glutathione) exhibit the nephroprotective activity by the criterion of survival of animals on various models of AKI. Glutathione demonstrates the best survival of animals with acute kidney injury of various genesis, while ademetionine has the lowest survival.

20. Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes // OfficialJ. of the Eur. Union. – 2010. – Vol. 53, Issue 276. – P. 33–80.